RESUMO
Introduction Trastuzumab-related cardiotoxicity has been a major concern in clinical practice, since observational studies have shown higher incidences than that reported in clinical trials. We aim to measure the incidence of trastuzumab-related cardiotoxicity in patients with early and metastatic breast cancer in the south of Brazil. Methods Multicenter prospective observational study, which included 109 patients with early or metastatic HER-2+ breast cancer undergoing any trastuzumab-based regimen. Cardiac events were measured by transthoracic echocardiography assessments and by signs and symptoms of heart failure. Results Trastuzumab-related cardiotoxicity was observed in 58 patients (53.2%). Emergency and hospitalization admissions were necessary in seven and three patients, respectively, due to symptoms of heart failure. One patient died in consequence of trastuzumab-related cardiotoxicity. In total, trastuzumab was discontinued in 31.2% of patients, of which almost a third could not return to treatment. In this study, no risk factors were significantly associated with the development of cardiotoxicity. Discussion The incidence of TRC and trastuzumab's early discontinuation observed was significantly higher in comparison with other studies. These findings endorse the fact that trastuzumab-related cardiotoxicity is a relevant adverse reaction, and therefore, cardiac dysfunction's monitoring must be highlighted in order to allow a safe use of trastuzumab in this population.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Trastuzumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cardiotoxicidade/diagnóstico por imagem , Ecocardiografia , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Receptor ErbB-2/metabolismoRESUMO
OBJECTIVE: Gaucher disease (GD) is a genetic disease caused by glucocerebrosidase deficiency. GD is treated by enzyme replacement therapy (ERT) with imiglucerase, a high-cost drug provided by the Brazilian Ministry of Health (BMH). This study reports the implementation of the BMH guidelines for GD in the southernmost state of the country. METHODS: We review the clinical and laboratorial data for patients seen at the reference center for GD from Rio Grande do Sul, Brazil (July 2003 to June 2006). RESULTS: Twenty-five patients were included in this study. At baseline, 19/20 were on ERT (mean dosage of imiglucerase = 51.8 U/kg/infusion), 3/17 presented anemia, and 5/16 thrombocytopenia. The amount of imiglucerase prescribed to these patients was adjusted according to the guidelines in July 2003; out of them, 18 were receiving ERT in the reference center at month 36 (mean dosage of imiglucerase = 27.5 U/kg/infusion), 2/18 presented anemia, and 4/18 presented thrombocytopenia. The analysis of the liver, spleen, and bone data presented some limitations, but the available information suggests that patients did not deteriorate. GD patients who initiated ERT after July 2003 (n = 5) received lower dosage of imiglucerase since the beginning of the treatment; most of them demonstrated clinical and laboratorial response. From baseline to month 36, the consumption of imiglucerase by the reference center showed a significant reduction, which represented savings of USD 3 million to the public health system. CONCLUSIONS: The model of care of GD patients suggested by the BMH guidelines appears to be cost-effective and could be an example for management of rare diseases in underdeveloped countries.
Assuntos
Terapia de Reposição de Enzimas , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Adolescente , Adulto , Brasil , Criança , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Guias de Prática Clínica como Assunto , Baço/efeitos dos fármacos , Baço/patologia , Inquéritos e QuestionáriosRESUMO
PURPOSE: To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil. METHODS: Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression. RESULTS: Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity. CONCLUSIONS: Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs.
Assuntos
Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/metabolismo , Fígado/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Acetilação , Arilamina N-Acetiltransferase/genética , Sequência de Bases , Brasil , Estudos de Coortes , Primers do DNA , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1% cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80%) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P < 0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.
Assuntos
Angioplastia Coronária com Balão , Arteriosclerose/terapia , Trombose/terapia , Animais , Endotélio Vascular/cirurgia , Masculino , CoelhosRESUMO
Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1 per cent cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80 per cent) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P<0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.